Ortho-formylated phenols and their derivatives are valuable intermediates in the chemical, pharmaceutical and mining industries. Therefore, processes for making hydroxyarylaldehydes, and in particular, 2-hydroxyarylaldehydes, have been well researched. It is well recognized that such hydroxyarylaldehydes can be made by reacting magnesium phenoxides with formaldehyde.
For instance, Casiraghi et al. described in J. C. S. Perkin I (1978) pp. 318 et seq. that aryloxymagnesium bromide alone or its complexes with hexamethylphosporamide (HMPA) can be reacted with formaldehyde in refluxing benzene and conclude that the absence of HMPA leads to the formation of dihydroxydiphenylmethanes whilst the formation of the desired 2-hydroxyarylaldehydes is promoted only by the presence of stoichiometric amounts of the HMPA ligand. This latter reaction is said to occur via an oxidation-reduction process, promoted by HMPA, between an intermediate 2-hydroxybenzyl alcohol intermediate and formaldehyde. The difference in acidity between the free and HMPA-complexed magnesium counterion is invoked to explain the two reaction pathways.
Similarly, Aldred et al. describe in J. C. S. Perkin I (1994) at pp. 1823 et seq. the deprotonation of phenols using magnesium methoxide, followed by distillative removal of free methanol and addition of paraformaldehyde to generate, by an ortho-specific magnesium-mediated formulation, the corresponding salicylaldehyde magnesium salts from which the salicylaldehydes are isolated by acidic work-up. They further disclose that addition of aqueous hydroxylamine sulphate to the salicylaldehyde magnesium salts, in place of the acid work-up, yields the corresponding salicylaldoximes.
Similar methods are also described in: U.S. Pat. No. 5,260,487 in which 2-hydroxyarylaldehyde is made by reacting a magnesium bis-hydrocarbyloxide, derived at least in part from a hydroxyaromatic compound having at least one free ortho position to the hydroxyl group with formaldehyde under substantially anhydrous conditions; and U.S. Pat. No. 5,354,920 in which 2-hydroxyarylaldehyde is made by reacting an aryloxymagnesium halide with formaldehyde under substantially anhydrous conditions in the presence of a polar organic solvent other than HMPA or 1,3-dimethyl-3,4,5,6-2(1H)-pyrimidone.
It has now been found and the present invention relates to a process in which 2-hydroxyarylaldehydes are made with an active species that contains only non-hydrocarbyloxy ligands attached to the magnesium aryloxide moiety.